HIV Tropism

[oksikoko]

I'm interested in HIV tropism, particularly dual tropism and am hoping someone here has a bit of information.

Most of us have CCR5-tropic strains, if I have this right. But there's also CXCR4-tropic. Some people have dual-tropic strains.

1) How does this interact with sensitivity to medications? If someone has a pan-sensitive strain, can that person's strain also be dual-tropic or are those mutually exclusive?

2) Would a person with a dual-tropic strain be able to take, say, Atripla, or are they restricted to special medications? Do they have any special needs?

3) Finally, do we know if outcomes and prognoses tend to be different based on mono- vs dual-tropism?

Thanks,
Lee

[eric48]

Hi, let me try to answer as I just did a bit of research on this.

I also took the CCR5 test on proviral DNA. It came out CCR5 + with no dual tropic or  X4 tropic. To which my doc commented that this is usual for people who have been treated early. He commented that such a test is valid for 2 years

3) if not HAART treated, X4 tropic patient have a faster progression of disease

2) a non 100% CCR5 tropism will only exclude Maraviroc as a possible med option (thus far the only approved in the CCR5 antagonist class). no influence on other classes so Atripla is OK

1) ditto: tropism has no influence on all classes of meds (with the obvious exception of above mentionned CCR5 antagonis)

I becomes more nad more common to have a tropism test before consiering treatment just to know if the CC5 antagonist class is an available option.
The more option you have the easier it makes to find the right treatment for you

Where I leave, CCR5 antagonist maraviroc is expensive nad reserved for people who have failed a first line treatment.

Me, I took the test just for fun. test results take one month.

Hope this helps

Eric

[oksikoko]

Hope this helps

Yes, sir. Thanks.

I'm asking because I have a friend whose strain is dual tropic, and I'm trying to help him with certain things. I didn't want to assume that what's true for me is true for him, and I'm ignorant on tropism issues. I hadn't considered having myself checked for this as you've done...

I would think they would have told me if my strain were dual or X4-tropic, but the doctor who did my genotyping was not particularly fond of 'people like me' and would've thought it was pointless telling me anything, probably. I'll ask my current doctor about it in September. One more thing to add to a growing list of questions. She's gonna hate me. She'll have just had a baby too, so maybe I should wait until December, haha.

FYI: I also did a little research and found this page helpful: http://www.prn.org/index.php/management/article/hiv_tropism_1002

Lee

[oksikoko]

This note from Physicians' Research Network is interesting: "X4-tropic virus emerges in about 50-60% of infected individuals with an average time to emergence of 5 years." It doesn't say whether that's in treated or untreated individuals, but it seems to be saying that via mutation, most of us will eventually have both X4- and R5-tropic strains running around in us. Having lots of X4 seems to be associated with worse outcomes.

Wild speculation from non-scientist-type person:
If this is only true of untreated individuals, it kind of makes sense: you're letting the virus mutate wildly with no interference, so you'll probably have all kinds of fun mutations there. X4-tropic strains could just pop up by stochastic evolution. I think.

In this hotlinked chart showing progression to AIDS, the solid line stands for CR5-only tropic while the dashed line is mixed (CR5 + X4) or dual (CR5/X4) tropic:


The page also says "Despite earlier reports, it appears that treatment responses to HAART are similar for persons infected with R5-using and X4-using virus, with the exception of regimens that include an R5 antagonist." Maraviroc, as Eric said, is an R5 antagonist.

That page also answers most of my other questions, but there sure are a lot of 'maybes' and 'probablys'.

[randomwalker]

Just curious...is hiv tropism routinely checked as part of the genotyping that is typically done before one starts meds, or is this a separate, more specialized test?

[tednlou2]

I researched this about 4 years ago.  I have already forgotten much of it.  If I don't continually have refreshers, it seems I don't retain the info.  Of course, that's often the case with most things. 

Is this saying if you hold off on meds, you'll likely develop dual tropism, and may have a harder time suppressing your virus, thus having possibly poorer outcome?  Or, will this just happen regardless? 

[oksikoko]

It looks like they're talking about all of us, treated and not.

"Studies have shown that approximately half of all infected individuals have detectable CXCR4 using virus over time. The probability of having X4-using virus is higher among antiretroviral experienced than treatment naïve persons infected with HIV; however, this observation may be largely accounted for by nadir CD4 counts."

[eric48]

Hi,

tropism test come in 2 forms
- on free RNA : a pre-requirement is that VL > 1000 (not commercially available where I live, when I started treatment)
- on proviral DNA OK even if UD, but available here only since mid 2012

They are expensive : ca. $1000, so unless a viral escape or med change is considered, then doc will not consider it

Once treatment is started and patient is adherent, viral replication (hence mutations) are virtually nihil. if the virus does not replicate (reproduce), it does not have kids, so does not mutate

This a bit theoretical and harsh statement, but, this is Pr Siliciano's views

In Vivo, there can be a bit of replication in some patients (event if UD)
therefore some mutations...which is why the test will not be valid forever.

Yet, under treatment, their is no proven effect on life expectancy because of the (rare) emergence of X4 tropism

Side note: why is it that most MSM have no kids, yet their number increases ? ;-)

Hope this helps

Eric